Aliphatically substituted thio- sulfinyl- and sulfonyl-alkyl-2,4,5-trihalogeno-imidazoles

ABSTRACT

2,4,5-trihalogeno-imidazoles substituted in 1-position at the imidazole nucleus by a group of the formula R-S-A-, R-SO-A- or RSO2- A- in which group R represents an optionally substituted aliphatic hydrocarbon radical and A represents an alkylene group, are described, which imidazoles are acaricidally active and at the same time well tolerated by cultivated plants; they are thus useful for the control of acarinae, and especially of spider mites, on cultivated plants and trees. Acaricidal compositions containing such novel imidazoles as active ingredients, and a method of controlling acarinae with the aid of such compounds are also disclosed.

United States Patent Inventors l-lans Rutz Basel; Kurt Gubler, Riehen, both of Switzerland Appl. No. 723,904 Filed Apr. 24,1968 Patented Dec. 7, 1971 Assignee Geigy Chemical Corporation Ardsley, N311. Priority Apr. 26, 1967 Switzerland 5960/67 ALIPHATICALLY SUBSTITUTED THIO- SULFTNYL- AND SULFONYL-ALKYL-2,4,5- TRlHALOGENO-IMIDAZOLES 6 Claims, No Drawings US. Cl 260/309, 424/273 C07d 49/36 References Cited UNITED STATES PATENTS 1/1969 Buchel et a1. 260/309 spec.) 260- 309 Netherlands Application 11 6,510,168 2- 1966 (14 pages spec.) 260- 309 Netherlands Application 111 6,609,596 1-1967 (pages 1- 6, 14- 23, 1 page drawing relied on) 260- 309 Primary Examiner-Natalie Trousof Anarneys Karl F. Jorda and F rederic-k H. Rabin ABSTRACT: 2,4,5-trihalogeno-imidazoles substituted in lposition at the imidazole nucleus by a group of the formula R- -S-A-, RSOA-- or R-SO -A in which group R represents an optionally substituted aliphatic hydrocarbon radical and A represents an alkylene group, are described, which imidazoles are acaricidally active and at the same time well tolerated by cultivated plants; they are thus useful for the control of acarinae, and especially of spider mites, on cultivated plants and trees. Acaricidal compositions containing such novel imidazoles as active ingredients, and a method of controlling acarinae with the aid of such compounds are also disclosed.

ALIPIIATICALLY SUBSTITUTED THIO- SULFINYL- AND SULFONYL-ALKYL-Z,4,5-TRIHALOGENO-IMIDAZOLES Hal wherein R represents an unsubstituted or substituted aliphatic hydrocarbon radical,

X represents sulfur or the sulfinyl or sulfonyl radical,

A represents an alkylene radical, and

Hal represents a halogen atom having an atomic number of at most 35.

The new imidazole derivatives of the general formula l are obtained according to the invention by reacting according to procedure a. a trihalogen imidazole of the general formula II I Hal 7 with an ether of the general formula III in which formulas Hal, R and A have the meanings given in formula I, in the presence of an acid binding agent; or by reacting according to procedure b. a trihalogen imidazole of the general formula IV Hal Hal l Hal W with a compound of the general formula V in which formulas Y and Z, with the exception of an S atom contained in either Y or Z, represent radicals which are split off in the reaction, and

Hal, R and A have the meanings given in formula I, p-

tionally in the presence of an acid binding agent;

and, if desired, oxidizing the end products of the general formula I, wherein X represents sulfur, to the corresponding sulfinyl or sulfonyl derivatives.

In the imidazole derivatives of general formula I, R, as aliphatic hydrocarbon radical can represent e.g. an alkyl radical having one to 16 carbon atoms, preferably however, a lower alkyl radical such as the methyl, ethyl, propyl, butyl or pentyl radicals, etc., also it can represent a lower alkenyl radical such as the allyl, crotyl or methallyl radical, or a lower alkinyl radical such as the propinyl or l-methyl-Z-propinyl radical. These hydrocarbon radicals can be monoor 'polysubstituted, e.g. by halogen, lower alkoxy, lower alkylthio or cyano groups. The chain of the alkylene radical A can be straight or branched and has, preferably, one or two carbon atoms as chain members. Preferred halogen atoms Hal are chlorine and, particularly, bromine.

Lower used in connection with an aliphatic radical means that the latter has at most four atoms.

As acid binding agents in the process according to procedures (a) and (b) of the invention, preferably inorganic bases such as hydroxides and oxides of alkali and alkaline earth metals, e.g. potassium or sodium hydroxide, as well as alcoholates of low alkanols with alkali metals such as sodium and potassium methylate, ethylate, propylate, isopropylate, butylate, particularly potassium tert. butylate, or mixtures of hydroxides and alcoholates are used. It is of advantage to perform the process according to procedures (a) and (b) in the presence of solvents or diluents which are inert to the reaction partners, i.e. hydrocarbons, halogenated hydrocarbons, amides such as dialkyl carboxylic acid amides, ethers and ether-type compounds, and also alcohols in the case of procedure (b).

In the process according to procedure (a) of the invention, advantageously the trihalogen imidazole of the general formula II is converted with one of the strong inorganic bases mentioned above into the corresponding imidazole salt. Because of its sensitivity to air, this is preferably reacted in an inert gas atmosphere, e.g. under nitrogen, with an ether of general formula III.

Of the symbols Y and Z in general formulas IV and V, one represents the mercapto group and the other a halogen atom, or one represents the group S-Me wherein Me is a metal atom and the other represents a halogen atom.

The oxidation of imidazole derivatives of the general formula 1, wherein X represents sulfur, to the corresponding sulfinyl or sulfonyl derivatives can be carried out with oxidizing agents such as hydrogen peroxide, organic peracids or potassium permanganate.

Some of the starting materials embraced by the general formulas I1 and IV are known and some are new. 2,4,5- Trichloroimidazole falling under the general formula ll can be prepared by reacting 2,4,5-tribromoirnidazole with HCl. The compound falling under the general formula IV in which e.g. I-Ial in 2-position is chlorine, and in 4- and 5-position is bromine, and in which YA- represents chloromethyl, can be prepared by reacting the hydroxymethyl-trihromo derivative with thionyl chloride in dimethyl formamide.

Some of the new imidazole derivatives are crystalline, others are oils. The new compounds are stable and dissolve well in the usual organic solvents. They are only slightly toxic to warm blooded animals.

The new imidazole derivatives of general formula I have acaricidal and insecticidal properties, especially very good acaricidal activity and are excellently suitable as acaricides in plant protection due to their nonphytotoxic properties for the control of acarinae and their stages of development.

The new active substances are suitable, e.g. for combating normally sensitive and resistant mites of the species Mesostigmata, Trombidiformes and Sarcoptiforrnes. For example, in the case of Tetranychidae, not only the mobile stages (larvae, protonymphs, deutonymphs and adults) but also the dormant stages and eggs are killed within a short time. On using lmethylthiomethyl-Z,4,5-tribromo-imidazole in a concentration of 0.05 percent, all stages, both mobile and dormant, of normally sensitive spider mites and of those which are resistant to phosphoric acid esters and benzilic acid esters are killed completely within 1 day.

Fruit trees treated with active substances of the general for mula I showed no phytotoxic effects after treatment, e.g. by spraying to runoff, with a suspension containing 0.5 g. of active substance per liter.

The imidazole derivatives of general formula I are applied in the form of solid or liquid compositions as dusts, sprinkling agents, granulates and aqueous dispersions which are obtained from wettable powders, pastes and emulsion concentrates. They are also applied as solutions or aerosols.

The compositions according to the invention are produced in the known way by intimately mixing and milling the active substance with suitable agriculturally acceptable planttolerated carriers, optionally with the addition of dispersing agents or solvents which are inert to the active substances and well tolerated by cultivated plants in the amounts applied to the latter in the field. The concentration of active substance in these compositions is e.g. 0.01-80 percent, preferably -80 percent, calculated on the total weight of the composition. The compositions according to the invention can be used together with other acaricidal, insecticidal, ovicidal, fungicidal, bactericidal compounds and/or with synergists or inactive additives. These concentrates can be diluted to give the desired concentrations for application.

The following nonlimitative examples illustrate the invention further. Where not otherwise expressly stated, parts and percentages are given by weight; the temperatures are given in degrees centigrade; parts by weight relate to parts by volume as grams to milliliters.

EXAMPLE 1 Six parts of potassium tert. butylate in 50 parts by volume of dimethyl formamide are added to a solution of 15.2 parts of 2,4,5-tribromo-imidazole in 50 parts by volume of dimethyl formamide. Five parts of methylthiomethyl chloride in 50 parts by volume of dimethyl formamide are added dropwise at room temperature to the clear yellow solution while stirring and introducing nitrogen. On completion of the addition, the reaction mixture is further stirred overnight at room temperature whereupon potassium chloride precipitates and the mixture becomes dark colored. The reaction mixture is diluted with 500 parts by volume of ether and extracted first with water and then with 2N sodium carbonate solution. No tribromoimidazole precipitates from the aqueous extract on acidifying. The ether phase is dried over sodium sulfate and concentrated in vacuo. The solid residue, l-methylthiomethyl- 2,4,5-tribromoimidazole, is boiled in alcoholic solution with animal charcoal. The solution is filtered hot. On cooling, 1- methylthiomethyl-2,4,5-tribromoimidazole precipitates from the filtrate in crystalline form, m.p. 9798.

EXAMPLE 2 a. One thousand and fifty-eight Parts of hydrogen chloride are introduced into a stirred solution of 890 parts of 2,4,5- tribromo-imidazole in 2,800 parts by volume of dimethyl formamide, the temperature being allowed to rise to 1 10 during the introduction. The reaction mixture is kept at 130 For 6 hours. On cooling to room temperature the solution solidifies, and the resulting slurry of crystals is charged into 15,000 parts of water. The solid product is filtered, washed with water and dried. Recrystallization from 50 percent aqueous alcohol yields 2,4,5-trichloroimidazole melting at l77280 with decomposition.

b. A solution of four parts of sodium hydroxide in 100 parts by volume of methanol is added to a solution of 17.1 parts of 2,4,5-trichloroimidazole in 100 parts by volume of methanol and the resulting solution is evaporated at 40 under water pump vacuum. The solid residue is slurried twice with 100 parts by volume of anhydrous benzene and the solvent evaporated in vacuo in order to remove any water adhering thereto. The dry sodium salt of trichloroimidazole is suspended in 300 parts by volume of anhydrous benzene. A solution of 10 parts of methylthiomethyl chloride in 100 parts by volume of benzene is added dropwise to the suspension at room temperature while stirring and introducing nitrogen, whereupon a slightly exothermic reaction takes place and the sodium salt of the trichloroimidazole dissolves and sodium chloride precipitates. The mixture is then stirred, first for 1 hour at room temperature, then for 1.5 hours at 60. After cooling, the reaction mixture is extracted with water and then with 2 N sodium carbonate solution to remove side products. After drying over sodium sulfate, the benzene phase is concentrated in vacuo. The residue is recrystallized from alcohol and the pure l-methylthiomethyl-2,4,5-trichloroimidazole thus obtained has a melting point of 72-73.

EXAMPLE 3 a. One hundred eighty parts of thionyl chloride are added dropwise to a stirred solution of 426 parts of l-hydroxymethyl-2,4,S-tribromoimidazole in 1,200 parts by volume of dimethyl formamide at a temperature of 0". The reaction mixture is stirred for 3 hours at room temperature and then for 1 hour at and, after recooling to room temperature, poured into 5,000 parts of water. The precipitated solid product is filtered, washed with water and dried. After recrystallization from benzene 1-chloromethyl-4,5-dibromo-2 -chloroimidazole is obtained, m.p. 86-87.

b. A solution of 5.6 parts of sodium thio-sec.butylate in 100 parts by volume of alcohol is added dropwise to a solution of 15.5 parts of 1-chloromethyl-4,5-dibromo-2-chloroimidazole in 100 parts by volume of anhydrous alcohol. The reaction mixture is allowed to stand overnight at room temperature. The solvent is then removed and the residue dissolved in ether/water. The ether phase is washed with water, dried over sodium sulfate and evaporated. 1-sec.butylthiomethyl-4,5- dibromo-Z-chloroimidazole is obtained in pure form from the oily residue by distillation; b.p. 1 13/0.00l mm. Hg.

EXAMPLE 4 A solution of 18.2 parts of l-methylthiomethyl-2,4,5- tribromoimidazole and 5.7 parts by volume of 30 percent aqueous hydrogen peroxide in 50 parts by volume of glacial acetic acid is allowed to stand at room temperature for 3 days. Upon dilution of the reaction mixture with water, the product separates as an oil. The mixture is neutralized with 2 N NaOH and the product is extracted with chloroform. The chloroform phase is washed with water, dried, and the solvent is evaporated in vacuo. The oily residue crystallizes upon trituration with methanol. Recrystallization from methanol affords pure l-methylsulphinylmethyl-2,4,5-tribromoimidazole, m.p. l20l2l.

EXAMPLE 5 A solution of 54.7 parts of 1-methylthiomethyl-2,4,5- tribromoimidazole and 80 parts by volume of 30 percent hydrogen peroxide in parts by volume of glacial acetic acid is heated at 70 for 1 hour. The reaction mixture is diluted with water, neutralized with sodium hydroxide, and the product is extracted with chloroform. The chloroform phase is washed with water, dried, and the solvent is evaporated. The oily residue crystallizes upon trituration with methanol. Recrystallization from methanol and benzene affords pure 1- methylsulphonylmethyl-Z,4,5-tribromoimidazo1e, m.p. l44l46.

The new 2,4,5-trihaloimidazole derivatives of the general formula 1 listed in the following table are obtained in the manner described in examples 1 to 5.

TABLE I 13.1. 146148/0.02 mm. H

B.P. 133135/0.01 mm. Hg.

B.P. 139-142/0.002 mm. Hg.

Bl. 129131/0.001 mm. Hg.

13.1. 133135/0.002 mm. Hg.

No. Compounds Physical constants 12 l-(2-b1'0m0ethyl)-thiomel;hyl-

2,4,5-tribromoimidazole.

l3 1-(Z-methyloxyethyl)-thiomethyl- 2,4,5-trtbromolmidazole.

l4. 1-(2-methylthi0ethyl)-thiornethyl- 2,4,5-tribromoimidazole.

l5. 1-(2-cyunocthyl)-thi0methyl- 2,4,5-tribromoimidazole.

16."- l-isopropylsulphinylmethyl- M.P. 107-109 2,4,5-tribromoimidazolc.

17 l-ethylsulphonylmethyl-2,4,5- M.P. 97-99 trlbromoimidazole.

l8. l-mcthylthiomethyli,5-dibrorn- Ml. Bil-101 2-chloroimidazole.

19 l-ethylthiomethyl-4,fi-dibromo- BI. 157-158/0.01 mm. Hg.

2-chloroirnidazole.

20 l-n-propylthiomethyl-4,5- m, 1.588.

dibromo-Z-chloroimidazole.

21 1-isopropylthiomcthyl-4,5- 13.1. 1ll/0.00l mm. Hg.

dibrorno-2-chloroimidazole.

22.... l-tert.butylthiomethyl-4,5- M.P. 63-65 dibromo-Z-chloroimidazole.

23. 1-ethylthiomethyl-2,4,5- Bl. 9496/0.01 mm. Hg.

trlchloroimidazole.

24. bn-propylthiomethyl-Z,4,5- B.P. 106108/0.0l mm. Hg.

trichloroimidazole.

25.. 1-isopropylthiomethyl-2,4,5- B.P. 127-128/0.06 mm. Hg.

trichloroimidazole.

26... 1-n-buty1thiomethyl-2,4,5- B.P. 1l5117/0.01 mm. Hg.

trichloroimidazole.

27.. 1-tert.butylthiomethyl-2,4,5- B.P. 115-117/0.01 mm. Hg.

trichlorolmldazole.

WETTABLE POWDER The following components are used to produce (a) a 50 per-' cent and (b) a 10 percent wettable powder: a.

50 parts of l-ethylthiomethyl-2,4,5-tribromoimidazole, parts of oleoylmethyl tauride sodium salt, 2.5 parts of disodium salt of dinaphthalene methane disulfonic acid, 25 parts of calcareous earth-clay silicates, and l7.5 parts of kaolin; b.

IO-parts of l'methylthiornethyl-2,4,5-tribromoimidazole,

3 parts of a mixture of the sodium salts of saturated fatty alcohol sulfonates (fatty alcohols=C,,C,,,),

5 parts of disodium salt of dinaphthalene methane disulfonic acid, and

82 parts of kaolin.

The amounts of active substance mentioned are intimately mixed with the additives in suitable mixers and milled in corresponding mills and rollers. Wettable powders are obtained which can be diluted with water to form suspensions of any concentration desired. Such suspensions are used chiefly for combatting acarinae on stone and pome fruit trees, citrus fruits, ornamental plants and shrubs, vegetables, and berry bushes.

EMULSION CONCENTRATE The following components are mixed together to produce a 25 percent emulsion concentrate:

25 parts of l-isopropylthiomethyl-2,4,5-tribromoimidazole,

parts of diacetone alcohol,

2 parts of iso-octyl-phen0xy polyoxyethylene-ethanol,

3 parts of emulsifier consisting of a mixture of the Ca salt of PASTE The following substances are used to produce a 45 percent paste:

45 parts of l-sec. butylthiomethyl-2,4,S-tribromoimidazole,

5 parts of sodium aluminum silicate,

14 parts of cetylpolyglycol ether (condensation product with 8 mols of ethylene oxide),

1 part of oleyl polyglycol ether (condensation product of oleyl alcohol and 5 mols of ehtylene oxide),

2 parts of spindle oil,

l0 parts of polyethylene glycol ether (Carbowax), and

23 parts of water.

The active substance is intimately mixed and milled with the additives in suitable apparatus. A paste is obtained from which, by dilution with water, suspensions of any concentration desired can be produced. Such suspensions are used, in particular, for controlling acarinae on. cultivated plants and ornamentals and also on fruit trees.

DUST

To produce a 10 percent dust,

10 parts of l-methylthiomethyl-2,4,5-trichloroimidazole,

5 parts of highly dispersed silicic acid, and

parts of talcum are intimately mixed. Such a dust can be used, e.g. to control acarinae on vegetables, ornamental plants and shrubs, and berry bushes.

TEST REPORT In order to determine the acaricidal properties of the new compounds, a test was carried out with bean leaves infected with red spider mites (Tetranychus urticae) and all stages of their development. The bean leaves were treated with aqueous emulsions in concentrations of 0.1; 0.05, 0.01 and 0.005 percent of active substance until completely wet (prepared from a 25 percent emulsion concentrate). The concentrations of active substance used which led to percent mortality after 6 days were determined.

Red spider mites which were normally sensitive and those resistant to benzilic acid esters and phosphoric acid esters were taken as test animals. The test results are given in the following table.

Concentration (in percent) of active substance leading to 100 mortality after 6 days Imagines/ Quiescent Compounds larvae stages Eggs l-methylthiomethyl-2,4,E-trlbromoimidazolc 0. 01 0. 05 0.01 l-ethylthiomethy1-2,4,5-tribromolmidazolc 0. 005 0. 005 0. 01 l-methylsulphinylmethyl-Z,4,5-

tribromoimldazole 0 01 0, O5 0, 1 l-methylsulphony1methyl-2,4,5-

trlbromoimldazole 0.01 O, 01 0.05 1-methy1-2,4,5-tr1brom oimidazole (known compound) 01. 05 0.05 0. 05

We claim: l. A compound ofthe formula Hall .l Hal RXA-N N l Hal wherein R represents alkyl of one to 16 carbon atoms; lower alkenyl; lower alkynyl; or lower alkyl substituted by a member selected from the group consisting of halogen, lower alkoxy, lower alkylthio and cyano; X represents --S-,

A represents alkylene of one or two carbon atoms; and

Hal represents a halogen atom having an atomic number of ethylthiomethyl-Z,4,5-tribromoimidazole.

almost 5. A compound as defined in claim 2, which is l-methyl- 2. A compound as defined in claim 1, wherein Hal sulphonylmethym4,54ribromoimidazole.

represents bromine and A represents -CH,.

3. A compound as defined in claim 2, which is lmethylthiomethyl-2,4,5-tribromoimidazole.

4. A compound as defined in claim 2, which is 1- 6. A compound as defined in claim 2, which is l-methylsulphinylmethyl-Z,4,5-tribromoimidazole. 

2. A compound as defined in claim 1, wherein Hal represents bromine and A represents -CH2-.
 3. A compound as defined in claim 2, which is 1-methylthiomethyl-2,4,5-tribromoimidazole.
 4. A compound as defined in claim 2, which is 1-ethylthiomethyl-2,4,5-tribromoimidazole.
 5. A compound as defined in claim 2, which is 1-methylsulphonylmethyl-2,4,5-tribromoimidazole.
 6. A compound as defined in claim 2, which is 1-methylsulphinylmethyl-2,4,5-tribromoimidazole.
 35. 